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Infectious diseases in sub-Sahara African pregnant women remain public health concerns. Malaria and curable sexually transmitted infections (STI) are the most common and severe infections causing poor pregnancy outcomes despite the several control programs implemented. Their coinfections could be frequent and more severe in pregnant women. The overall objective of our thesis was to contribute to improving the control of these co-infections through describing their prevalence, identifying risk groups, determining their impact on the pregnancies, and identifying the effective strategies for their control. We analyzed retrospectively captured routine data and we carried out a cross-sectional study in rural settings of Burkina Faso. We found that malaria and curable STI coinfections are frequent in pregnant women but are underdiagnosed in routine care in rural peripheral health facilities. Pregnant women who received no IPT-SP presented more frequently with coinfections. Malaria and curable STIs considered separately were more frequent in students. Miscarriages and stillbirth were associated with symptomatic coinfections contrary to low birth weight, and preterm births. Our findings have shown for the first time the severe impact of malaria and curable STI co-infections in pregnant women. IPT-SP should be reinforced in pregnant women. Health education should be set up for young girls to prevent complications in teenagers’ pregnancies., (MED - Sciences médicales) -- UCL, 2022

Despite occasional reports of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy, the question of placental infection and its consequences for the newborn remain unanswered. Herein, we analyzed the placentas of 31 coronavirus disease 2019-positive mothers by reverse transcriptase PCR, immunohistochemistry, and in situ hybridization. Only one case of placental infection was detected, which was associated with intrauterine demise of the fetus. Differentiated primary trophoblasts were then isolated from nonpathologic human placentas at term, differentiated, and exposed to SARS-CoV-2 virions. Unlike for positive control cells Vero E6, the virus inside cytotrophoblasts and syncytiotrophoblasts or in the supernatant 4 days after infection was undetectable. As a mechanism of defense, we hypothesized that trophoblasts at term do not express angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), the two main host membrane receptors for SARS-CoV-2 entry. The quantification of these proteins in the placenta during pregnancy confirmed the absence of TMPRSS2 at the surface of the syncytium. Surprisingly, a transiently induced experimental expression of TMPRSS2 did not allow the entry or replication of the virus in differentiated trophoblasts. Altogether, these results underline that trophoblasts are not likely to be infected by SARS-CoV-2 at term, but raise concern about preterm infection.

BACKGROUND: The placenta is the functional interface between the mother and the fetus during pregnancy, and a critical determinant of fetal growth and life-long health. In the first trimester, it develops under a low-oxygen environment, which is essential for the conceptus who has little defense against reactive oxygen species produced during oxidative metabolism. However, failure of invasive trophoblasts to sufficiently remodel uterine arteries toward dilated vessels by the end of the first trimester can lead to reduced/intermittent blood flow, persistent hypoxia and oxidative stress in the placenta with consequences for fetal growth. Fetal growth restriction (FGR) is observed in ∼10% of pregnancies and is frequently seen in association with other pregnancy complications, such as preeclampsia (PE). FGR is one of the main challenges for obstetricians and pediatricians, as smaller fetuses have greater perinatal risks of morbidity and mortality and postnatal risks of neurodevelopmental and cardio-metabolic disorders. OBJECTIVE AND RATIONALE: The aim of this review was to examine the importance of placental responses to changing oxygen environments during abnormal pregnancy in terms of cellular, molecular and functional changes in order to highlight new therapeutic pathways, and to pinpoint approaches aimed at enhancing oxygen supply and/or mitigating oxidative stress in the placenta as a mean of optimizing fetal growth. SEARCH METHODS: An extensive online search of peer-reviewed articles using PubMed was performed with combinations of search terms including pregnancy, placenta, trophoblast, oxygen, hypoxia, high altitude, FGR and PE (last updated in May 2020). OUTCOMES: Trophoblast differentiation and placental establishment are governed by oxygen availability/hypoxia in early pregnancy. The placental response to late gestational hypoxia includes changes in syncytialization, mitochondrial functions, endoplasmic reticulum stress, hormone production, nutrient handling a

The placenta is a multifaceted organ, fulfilling critical functions for the fetus and the mother. Therefore, it is a critical regulator of the pregnancy, and its dysfunction leads to diseases, including fetal growth restriction and preeclampsia. Studying the placenta is a difficult task since its existence is transient, and its structure is specific to our species. In vitro differentiation of primary cytotrophoblast isolated from term human placenta has been widely used in the placental research field as it represents a reliable model to study cellular differentiation and function. Direct alternatives include trophoblastic cell lines, explants, and organoids, but this protocol, based on the separation of the cells on a Percoll gradient, presents the advantage of being relatively cheap and easy to perform in every research laboratory. Furthermore, the 2D culture is a flexible method that can be adapted to various experimental conditions (transfection, drug exposure, metabolic study, observations, etc.), allowing mechanistic explorations of cellular processes.

BACKGROUND: The diagnosis of cervical insufficiency is based on the previous history of recurrent second or early third trimester losses. Its incidence among pregnant women is 0.5-1% but can be as high as 75% among women with preterm birth. Transvaginal cerclage (TVC) is the common therapy of cervical insufficiency. However, this technique has several limits, especially in twin pregnancies. As some selected conditions, a transabdominal cerclage (TAC) is indicated, it has been offered to patients with multiple pregnancies. AIM: To evaluate the outcomes of twin pregnancies with transabdominal cerclage in terms of preterm birth rate and neonatal morbidity and mortality. MATERIALS AND METHODS: We conducted a retrospective study of seven patients with twin pregnancies managed with transabdominal cerclage at the end of the first trimester (12-15 weeks). We selected patients with a history of fetal loss who met the indications criteria of TAC (history of TVC failure or short cervix unable to have TVC). The antenatal and delivery data were collected and compared to those of their previous pregnancy. OUTCOMES: All patients carried their pregnancy throughout the second trimester and delivered during the third trimester. Mean gestational age was 34 4/7 week. All newborns were alive and neonatal morbidity rate was 50%, mostly related to preterm birth. Mean duration of neonatal intensive care stay was 32 days. There were no operative complications following TAC. CONCLUSIONS: Perinatal outcomes are considerably improved in twin pregnancies with transabdominal cerclage. Our findings corroborate those of previous case reports and support the efficacy of TAC for managing cervical insufficiency in twin pregnancies.

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P<0.001) and had a lower prevalence of cerebrovascular FMD (30% versus 52%; P=0.003) but underwent more often renal revascularization (63% versus 40%, P<0.001). In conclusion, the prevalence of pregnancy-related complications such as gestational hypertension and preterm birth was high in patients with FMD, probably related to the severity of renal FMD. However, the prevalence of preeclampsia and arterial complications was low/moderate. These findings emphasize the need to screen hypertensive women for FMD to ensure revascularization before pregnancy if indicated and appropriate follow-up during pregnancy, without discouraging patients with FMD from considering pregnancy.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe and potentially fatal syndrome that can occur during pregnancy. A 36 years-old woman, at 29 weeks of gestation, presented with itchiness and jaundice since a week. On clinical examination she was apyrexial and frankly icteric. Laboratory data showed evidence of acute hepatitis. A complete work-up was made excluding viral hepatitis (HAV, HEV, HBV, HCV, HHV6, CMV, EBV) and autoimmune liver disease. Liver diseases related to pregnancy were not completely excluded. A liver biopsy was performed and firstly interpreted as showing features of acute hepatitis. The clinical situation worsened, she developed fever with signs of fetal distress and emergent delivery was done. A second look at the liver biopsy showed features compatible with HLH, which was also confirmed on bone marrow biopsy. Extensive work-up with exclusion of infectious and malignant diseases, lead us to the diagnosis of HLH secondary to pregnancy and short term steroid therapy was started. She then completely recovered and didn't present any relapse after 4 months of follow up. HLH during pregnancy is very rare and this is the first case of HLH presenting as acute hepatitis and diagnosed on a liver biopsy.

STUDY QUESTION: Are hypoxia-inducible factors (HIF) responsible for the potentiation of inhibin alpha subunit (INHA) gene expression in primary cultures of human term cytotrophoblasts under low-oxygen tension? SUMMARY ANSWER: Both HIF1A and endothelial PAS domain protein 1 (EPAS1) are involved in the potentiation of INHA gene upregulation in cytotrophoblasts cultured under hypoxia. WHAT IS KNOWN ALREADY: During the in vitro differentiation of cytotrophoblasts into syncytiotrophoblasts under 21% O2, INHA expression increases. This expression is further increased when cells are cultured under low-oxygen tension (e.g. 2.5% O2). Moreover, in pregnancy-related diseases, such as pre-eclampsia or intrauterine growth restriction (IUGR), in which hypoxia is suspected to be responsible for the abnormal placental development, maternal serum concentration of inhibin A is elevated. STUDY DESIGN, SIZE, DURATION: Cytotrophoblasts were isolated and purified from human term placentas (n = 6). Cells were cultured under 21% O2, and allowed to differentiate for 48 h. A first group of cells was treated for 16 h under 21% O2 with dimethyloxalylglycine (DMOG) or deferoxamine (DFX), molecules that mimic hypoxia by inhibiting HIF1 proteasomal degradation. Involvement of HIF1A and EPAS1 (also known as HIF2A), two HIF isoforms expressed in trophoblasts, was shown by treating another group of cells cultured under 2.5% O2 with specific inhibitors of HIF1A and EPAS1 for 16 h. INHA mRNA expression was assessed by real-time PCR and secreted inhibin A was quantified by ELISA. The role of HIF1A and EPAS1 in INHA transcriptional regulation was further confirmed by cotransfecting primary cytotrophoblasts with a luciferase reporter plasmid containing a 3.9 kb INHA promoter and plasmids allowing overexpression of HIF1A and EPAS1. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placentas were obtained after vaginal or elective cesarean delivery from uncomplicated pregnancies at term (n≥ 4). The methods used we

To compare perinatal outcomes following emergency cerclage between patients with singleton pregnancies with prolapsed and non-prolapsed membranes. The present retrospective cohort study included data from women who underwent physical examination-indicated emergency cerclage at between 15 and 25 weeks of pregnancy at Saint Luc University Hospital, Brussels, Belgium, between January 1, 2000, and December 31, 2014. Outcomes were compared based on the presence of prolapsed or non-prolapsed membranes. The primary outcome measures were the duration of pregnancy at delivery and the interval between cerclage and delivery. Secondary outcomes included delivery weight, fetal or neonatal death, and neonatal morbidity, including neonatal intensive care unit admission. Data were included from 140 patients with cervical dilation of at least 1 cm; 85 women had non-prolapsed membranes and 55 women had prolapsed membranes. Among patients with non-prolapsed membranes, the mean duration of pregnancy at delivery was later (P<0.001), the latency between cerclage and delivery was longer (P<0.001), neonatal survival was higher (P=0.036), mean delivery weight was higher (P<0.001), the prevalence of preterm delivery was lower (P<0.001), and severe neonatal morbidity and neonatal intensive care unit admission were lower (P<0.001). Having non-prolapsed membranes was associated with improved perinatal outcomes following emergency cerclage.

OBJECTIVE: The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. METHODS: Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. RESULTS: Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). CONCLUSION: The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant.